CA1296735C - Platinum(ii) complexes of 2,3-dimercapto-2-butene- dinitrilate(2-)-s,s' derivatives and process for their production - Google Patents
Platinum(ii) complexes of 2,3-dimercapto-2-butene- dinitrilate(2-)-s,s' derivatives and process for their productionInfo
- Publication number
- CA1296735C CA1296735C CA000543164A CA543164A CA1296735C CA 1296735 C CA1296735 C CA 1296735C CA 000543164 A CA000543164 A CA 000543164A CA 543164 A CA543164 A CA 543164A CA 1296735 C CA1296735 C CA 1296735C
- Authority
- CA
- Canada
- Prior art keywords
- platinum
- dimercapto
- butene
- dinitrilate
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical class [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 4
- 238000000034 method Methods 0.000 title claims 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229910002621 H2PtCl6 Inorganic materials 0.000 description 2
- 229910020437 K2PtCl6 Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- FLPZQPUGOOVZHK-UHFFFAOYSA-N 1,2-dichlorocycloocta-1,5-diene platinum Chemical compound [Pt].ClC1=C(Cl)CCC=CCC1 FLPZQPUGOOVZHK-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 101100285903 Drosophila melanogaster Hsc70-2 gene Proteins 0.000 description 1
- 229910020427 K2PtCl4 Inorganic materials 0.000 description 1
- 229910019032 PtCl2 Inorganic materials 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- JMXMXKRNIYCNRV-UHFFFAOYSA-N bis(hydroxymethyl)phosphanylmethanol Chemical compound OCP(CO)CO JMXMXKRNIYCNRV-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE:
Platinum (II) complexes of 2,3-dimercapto-2-butene-dinitrilate(2-)-S,S' derivatives having the general formula (I):
( I ) wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain hydroxyl groups and has 1 to 2 carbon atoms, are useful for treating tumor diseases.
A process for preparing these compounds and to pharmaceutical compositions containing these compounds is also disclosed.
Platinum (II) complexes of 2,3-dimercapto-2-butene-dinitrilate(2-)-S,S' derivatives having the general formula (I):
( I ) wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain hydroxyl groups and has 1 to 2 carbon atoms, are useful for treating tumor diseases.
A process for preparing these compounds and to pharmaceutical compositions containing these compounds is also disclosed.
Description
~29~735;
The present invention relates to platinum(II) complexes of 2,3-dimercapto-2-butene-dinitrilate(2-)-S,S' derivatives of the general formula (I):
R\ S ~ CN
Pt(II~
R S CN
wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain hydroxyl groups or not and has 1 to 2 carbon atoms, as well as to a process for pre-paring the same and to pharmaceutical compositions contain-ing these compounds.
The compounds of the present invention are prepared~ inaecordanee with the below seheme, from the respective cis-dichloro platinum(II) bis-substituted intermediates of the general formula (II):
is-[pt(II)cl2~Rl2] (II) wherein R is as defined for (I), and from the metallic cis-1,2-dicyano-1,2-athylenedithiolate of general formula (III):
C i S - [P t ( I I ) C 1 2f R 1 2 ] ~ X ~ .X
MS C~ ~ \S CN
(II) (III) (I) wherein M is a monovalent metal.
:
: The above reactions occur suitably at room temperature, and a ketone or an alcohol having 1 to 4 carbon atoms may be used as solvents; acetone and methanol are preferred, al-.
: 35 though other ketorles or alcohols having 1 to 4 four carbon atoms are also acceptable for this reaction. The end prod-- -2~ 3~
ucts thus obtained are purified by crystallization or simply by washing the formed precipitate.
Respective cis-dichloro platinum(II) bis-substituted pre-cursors of the general formula (II) are obtained by conven-tional methods when R is a dialkylsulphide or trialkylphos-phine group without hydroxyl groups (Kauffman,GB and Cowan, D0: Inorg.Synth.(1963),7,239-245; Kauffman,GB and Cowan,D0:
Ibid (1960),6,211-215; Parshall,GW: Ibid (1970),12,26-33) according to the ~ollowing reactions:
Pt ~ H2PtCl6 + nitrous gases H2PtCl6 + KCl K2PtCl6 + ~Cl K2PtCl6 + C24K2 ~ 2 4 2C02 ~ 2KCl K2PtCl4 ~ 2(H5C2)2S -b trans-[PtCl2~H5C2)2S}2] ~ 2KCl tranS-[ptcl2~(H5c2)2s~2] ~ 2(~l5c2)2 [ { 5 2 ~ ~3 [ptf(H5~2)2s~4~cl2 ~ ciS-[ptcl2{(Hsc2)2sl2] ( 5 2)2 K PtC14 ~ 2(H5C2)3P ~cis-[ptcl2f(H5c2)3 ~2]
When R is a trialkylphosphine group with hydroxyl groups, the corresponding cis-dichloro platinum(II) bis-substituted precursor may be advantageously obtained by reacting tris-hydroxyalkylphosphine with dichloro-1,5-cyclooctadiene platinum (Spanish Patent of Addition No. 548,849). Metallic cis-1,2-dicyano-1,2-~thylenedithiolates of general formula (III) are obtained from the corresponding cyanide.
Thus, sodium cis-1,2-dicyano-1,2-ethylenedithiolate (III, M= Na) is also obtained by conventional methods: sodium cyanide is reacted with carbon disulphide and N,N~dimethyl-formamide (Bahr,G and Schleitzer,G: Chem.Ber.(1957),90,438) ' ':
- ~ -12! ?&i7:~5 according to the following reaction:
NaCN + CS2 + 3HCON(CH3)2 --~vNccs2Nao3HcoN(cH3)2 (monomer) followed by dimerization (Locke,J and McCleverty,OA: Inorg.
Chem.(1966),5,1157) according to the following reaction:
NaS _ ,~CN
2 NCCS2Na. 3 HCON(CH3)2 Cl3CH l +
NaS CN
6 HCON(CH3)2 + 2 S
; 15 The compounds of the present invention are useful as a medication in the treatment of tumor~ and may be adminis-tersd, mixed with suitable CQrriers~ orally in ths ~orm of tablets, capsules, coated-tablets, granules, syrup, solu-tion, etc., or by injection, at daily doses ranging from 10 to 600 mg/m2.
.
A number of examples will now be described in non-limita-tive manner to illustrate the invention.
' , :: .
The present invention relates to platinum(II) complexes of 2,3-dimercapto-2-butene-dinitrilate(2-)-S,S' derivatives of the general formula (I):
R\ S ~ CN
Pt(II~
R S CN
wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain hydroxyl groups or not and has 1 to 2 carbon atoms, as well as to a process for pre-paring the same and to pharmaceutical compositions contain-ing these compounds.
The compounds of the present invention are prepared~ inaecordanee with the below seheme, from the respective cis-dichloro platinum(II) bis-substituted intermediates of the general formula (II):
is-[pt(II)cl2~Rl2] (II) wherein R is as defined for (I), and from the metallic cis-1,2-dicyano-1,2-athylenedithiolate of general formula (III):
C i S - [P t ( I I ) C 1 2f R 1 2 ] ~ X ~ .X
MS C~ ~ \S CN
(II) (III) (I) wherein M is a monovalent metal.
:
: The above reactions occur suitably at room temperature, and a ketone or an alcohol having 1 to 4 carbon atoms may be used as solvents; acetone and methanol are preferred, al-.
: 35 though other ketorles or alcohols having 1 to 4 four carbon atoms are also acceptable for this reaction. The end prod-- -2~ 3~
ucts thus obtained are purified by crystallization or simply by washing the formed precipitate.
Respective cis-dichloro platinum(II) bis-substituted pre-cursors of the general formula (II) are obtained by conven-tional methods when R is a dialkylsulphide or trialkylphos-phine group without hydroxyl groups (Kauffman,GB and Cowan, D0: Inorg.Synth.(1963),7,239-245; Kauffman,GB and Cowan,D0:
Ibid (1960),6,211-215; Parshall,GW: Ibid (1970),12,26-33) according to the ~ollowing reactions:
Pt ~ H2PtCl6 + nitrous gases H2PtCl6 + KCl K2PtCl6 + ~Cl K2PtCl6 + C24K2 ~ 2 4 2C02 ~ 2KCl K2PtCl4 ~ 2(H5C2)2S -b trans-[PtCl2~H5C2)2S}2] ~ 2KCl tranS-[ptcl2~(H5c2)2s~2] ~ 2(~l5c2)2 [ { 5 2 ~ ~3 [ptf(H5~2)2s~4~cl2 ~ ciS-[ptcl2{(Hsc2)2sl2] ( 5 2)2 K PtC14 ~ 2(H5C2)3P ~cis-[ptcl2f(H5c2)3 ~2]
When R is a trialkylphosphine group with hydroxyl groups, the corresponding cis-dichloro platinum(II) bis-substituted precursor may be advantageously obtained by reacting tris-hydroxyalkylphosphine with dichloro-1,5-cyclooctadiene platinum (Spanish Patent of Addition No. 548,849). Metallic cis-1,2-dicyano-1,2-~thylenedithiolates of general formula (III) are obtained from the corresponding cyanide.
Thus, sodium cis-1,2-dicyano-1,2-ethylenedithiolate (III, M= Na) is also obtained by conventional methods: sodium cyanide is reacted with carbon disulphide and N,N~dimethyl-formamide (Bahr,G and Schleitzer,G: Chem.Ber.(1957),90,438) ' ':
- ~ -12! ?&i7:~5 according to the following reaction:
NaCN + CS2 + 3HCON(CH3)2 --~vNccs2Nao3HcoN(cH3)2 (monomer) followed by dimerization (Locke,J and McCleverty,OA: Inorg.
Chem.(1966),5,1157) according to the following reaction:
NaS _ ,~CN
2 NCCS2Na. 3 HCON(CH3)2 Cl3CH l +
NaS CN
6 HCON(CH3)2 + 2 S
; 15 The compounds of the present invention are useful as a medication in the treatment of tumor~ and may be adminis-tersd, mixed with suitable CQrriers~ orally in ths ~orm of tablets, capsules, coated-tablets, granules, syrup, solu-tion, etc., or by injection, at daily doses ranging from 10 to 600 mg/m2.
.
A number of examples will now be described in non-limita-tive manner to illustrate the invention.
' , :: .
3~i E_x a m p l e Platinum(II)[2,3-dimercapto-2-butene-dinitrilate (2-)-S,S']bis(diethylsulphide) A mixture of 0.5 9 (1.12 mmole) of cis-[Pt(II)Cl2{5(CH2CH3)2¦2]
and 0 2085 9 (1.12 mmole) of sodium cis-1,2-dicyano-1,2-ethylenedithiolate was dissolved in 100 ml of acetone, then the yellow-coloured solution changed to orange. The solution was filtered off and the liquid was concentrated to give reddish-orange crystals which were recrystallized from acetone.
Yield: 0.31 9 (53.7%).
Melting point: 141-145QC.
IR Spectrum (K8r) cm 1: 2960, 2930, 2865, 2205, 1495, 1440, 1430, 1370, 1275, 1250, 1152, 1105, 1075, 1045, 970, 780, 510.
NMR Spectrum (CD3COCD3) ~: 3.4-1.75 (m), 1.5-1.2 (t).
E x a m p l e 2 Platinum(II)r2,3-dimercapto-2-butene-dinitrilats (2-)-S,S']bis(triethylphosphine) 0.1853 9 (1.0 mmole) of sodium cis-1,2-dicyano-1,2-ethylene-dithiolate were dissolved in 100 ml of methanol and 0.5 9 30 (1.0 mmole) of cis-[Pt(I )Cl2{P(CH2CH3)332] were added- The ; yellowish solution ~aded and turned turbid. The solution was filtered off and the precipitate washed with methanol, and then dried. 0.3 9 of pale-red product was obtained.
Yield: 54%.
Melting point: 230-232C.
,.~
735;
IR Spectrum (K3r) cm 1: 2970, 2930, 2870, 2200, 1496, 1450, 1415, 1380, 1250, 1150, 1038, 765, 728, 638, 515.
NMR Spectrum (CD3COCD3)~ : 2.6-1.9 (m), 1.4-0 9 (m).
E x a m p l e 3 Platinum(II)[2,3-dimercapto-2-butene-dinitrilate (2-)-S,Si]bis(tris-hydroxymethylphosphine) 0.3 9 (1.16 mmole) of sodium cis-1,2-dicyano-1,2-ethylene-dithiolate were dissolved in 100 ml of methanol and 0.83 9 (1.16 mmole) of cis-LPt(II)Cl~{P(CH20H)3~2] were added. The yellow-coloured solution changed to or~n9e. The solution was concentrated and left to crystallize. The so}id obtainsd was dissolved in acetone. The soluble phase in acetone was dried and recrystallized ~rom methanol to give dark-red crystals.
Yield: 0.81 9 (86~).
Melting point: 203-206-C.
IR Spectrum (K8r) cm : 3600-2900, 2220, 1690, 1505, 1438, 1160, 1035, 8B5, 840.
NMR (CD30D) ~: 4.9-4.3 (t) 0= 24.4Hz.
~`,
and 0 2085 9 (1.12 mmole) of sodium cis-1,2-dicyano-1,2-ethylenedithiolate was dissolved in 100 ml of acetone, then the yellow-coloured solution changed to orange. The solution was filtered off and the liquid was concentrated to give reddish-orange crystals which were recrystallized from acetone.
Yield: 0.31 9 (53.7%).
Melting point: 141-145QC.
IR Spectrum (K8r) cm 1: 2960, 2930, 2865, 2205, 1495, 1440, 1430, 1370, 1275, 1250, 1152, 1105, 1075, 1045, 970, 780, 510.
NMR Spectrum (CD3COCD3) ~: 3.4-1.75 (m), 1.5-1.2 (t).
E x a m p l e 2 Platinum(II)r2,3-dimercapto-2-butene-dinitrilats (2-)-S,S']bis(triethylphosphine) 0.1853 9 (1.0 mmole) of sodium cis-1,2-dicyano-1,2-ethylene-dithiolate were dissolved in 100 ml of methanol and 0.5 9 30 (1.0 mmole) of cis-[Pt(I )Cl2{P(CH2CH3)332] were added- The ; yellowish solution ~aded and turned turbid. The solution was filtered off and the precipitate washed with methanol, and then dried. 0.3 9 of pale-red product was obtained.
Yield: 54%.
Melting point: 230-232C.
,.~
735;
IR Spectrum (K3r) cm 1: 2970, 2930, 2870, 2200, 1496, 1450, 1415, 1380, 1250, 1150, 1038, 765, 728, 638, 515.
NMR Spectrum (CD3COCD3)~ : 2.6-1.9 (m), 1.4-0 9 (m).
E x a m p l e 3 Platinum(II)[2,3-dimercapto-2-butene-dinitrilate (2-)-S,Si]bis(tris-hydroxymethylphosphine) 0.3 9 (1.16 mmole) of sodium cis-1,2-dicyano-1,2-ethylene-dithiolate were dissolved in 100 ml of methanol and 0.83 9 (1.16 mmole) of cis-LPt(II)Cl~{P(CH20H)3~2] were added. The yellow-coloured solution changed to or~n9e. The solution was concentrated and left to crystallize. The so}id obtainsd was dissolved in acetone. The soluble phase in acetone was dried and recrystallized ~rom methanol to give dark-red crystals.
Yield: 0.81 9 (86~).
Melting point: 203-206-C.
IR Spectrum (K8r) cm : 3600-2900, 2220, 1690, 1505, 1438, 1160, 1035, 8B5, 840.
NMR (CD30D) ~: 4.9-4.3 (t) 0= 24.4Hz.
~`,
Claims (6)
1. A platinum (II) complex of a 2,3-dimercapto-
2-butene-dinitrilate(2-)-S,S' derivative of the general formula (I):
(I) wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain at least one hydroxyl group and has 1 to 2 carbon atoms.
2. A process for preparing a compound according to claim 1, comprising:
- reacting a compound of general formula (II):
(II) wherein R is as defined in claim 1, with a compound of general formula (III):
(III) wherein M is a monovalent metal, in the presence of a ketone or an alcohol having 1 to 4 carbon atoms as solvent; and - crystallization or washing of the formed precipitate.
(I) wherein R is a dialkylsulphide or trialkylphosphine group and each alkyl group may contain at least one hydroxyl group and has 1 to 2 carbon atoms.
2. A process for preparing a compound according to claim 1, comprising:
- reacting a compound of general formula (II):
(II) wherein R is as defined in claim 1, with a compound of general formula (III):
(III) wherein M is a monovalent metal, in the presence of a ketone or an alcohol having 1 to 4 carbon atoms as solvent; and - crystallization or washing of the formed precipitate.
3. A process according to claim 2, wherein M is sodium.
4. A process according to claim 2, wherein the ketone used as solvent is acetone.
5. A process according to claim 2, wherein the alcohol used as solvent is methanol.
6. A pharmaceutical composition comprising at least one of the compounds of claim 1, together with at least one pharmaceutical carrier or adjuvant.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES8601525 | 1986-08-04 | ||
| ES8601525A ES2000614A6 (en) | 1986-08-04 | 1986-08-04 | Complexes of platinum (II) 2,3-dinitrilo-2-butene-2,3-dithiolate, a process for preparing them and pharmaceutical compositions containing them. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1296735C true CA1296735C (en) | 1992-03-03 |
Family
ID=8248116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000543164A Expired - Fee Related CA1296735C (en) | 1986-08-04 | 1987-07-28 | Platinum(ii) complexes of 2,3-dimercapto-2-butene- dinitrilate(2-)-s,s' derivatives and process for their production |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0258655B1 (en) |
| JP (1) | JPS6341489A (en) |
| CA (1) | CA1296735C (en) |
| DE (1) | DE3774373D1 (en) |
| ES (1) | ES2000614A6 (en) |
| PH (1) | PH23809A (en) |
| ZA (1) | ZA875344B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR940010295B1 (en) * | 1991-07-05 | 1994-10-22 | 한국과학기술연구원 | New anti-cancerous pt-complex derivatives and process for the preparation thereof |
| JP3849005B2 (en) * | 2000-03-08 | 2006-11-22 | 独立行政法人産業技術総合研究所 | Platinum complexes useful as sensitizers |
| DE60219621T2 (en) * | 2002-08-29 | 2007-12-20 | Jih-Ru Hwu | Organometallic complex |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1274529A (en) * | 1985-09-05 | 1990-09-25 | Federico Sampedro | Platinum(ii) complexes of 1,1-cyclobutane- dicarboxylate and process for their production |
-
1986
- 1986-08-04 ES ES8601525A patent/ES2000614A6/en not_active Expired
-
1987
- 1987-07-21 ZA ZA875344A patent/ZA875344B/en unknown
- 1987-07-28 CA CA000543164A patent/CA1296735C/en not_active Expired - Fee Related
- 1987-08-03 DE DE8787111190T patent/DE3774373D1/en not_active Expired - Fee Related
- 1987-08-03 EP EP87111190A patent/EP0258655B1/en not_active Expired - Lifetime
- 1987-08-03 PH PH35616A patent/PH23809A/en unknown
- 1987-08-03 JP JP62192763A patent/JPS6341489A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE3774373D1 (en) | 1991-12-12 |
| ES2000614A6 (en) | 1988-03-01 |
| EP0258655A2 (en) | 1988-03-09 |
| ZA875344B (en) | 1988-01-27 |
| JPS6341489A (en) | 1988-02-22 |
| EP0258655A3 (en) | 1989-05-24 |
| EP0258655B1 (en) | 1991-11-06 |
| PH23809A (en) | 1989-11-23 |
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